A Chaperone System for Glycoprotein Folding: The Calnexin/Calreticulin Cycle

Abstract

The endoplasmic reticulum (ER) contains a particularly wide range of molecular chaperones and other proteins that assist the folding and quality control of newly synthesized protein. Some, like BiP/GRP78 and GRP94, belong to classical chaperone families. Others, like protein disulfide isomerase, ERp57, and ERp72, belong to the family of thiol-disulfide oxidoreductases especially well represented in the ER. The ER lectin chaperones calnexin (CNX) and calreticulin (CRT) have unique features that distinguish them from other known molecular chaperones. They interact with proteins that carry N-linked glycans, and cooperate with a number of accessory enzymes during the folding process. Here we review work on calnexin/calreticulin-assisted glycoprotein folding in the ER, with an emphasis on recent molecular and structural studies.